Title

Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE

Student Author(s)

Cherilyn M. Sirois

GSBS Program

Interdisciplinary Graduate Program

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Date

5-1-2007

Document Type

Article

Medical Subject Headings

Animals; Antigen-Antibody Complex; Antigens, Neoplasm; B-Lymphocytes; CpG Islands; DNA-Binding Proteins; Dendritic Cells; HMGB1 Protein; Lupus Erythematosus, Systemic; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Oligodeoxyribonucleotides; Receptors, Cell Surface; Toll-Like Receptor 9

Disciplines

Immunology and Infectious Disease | Life Sciences | Medicine and Health Sciences

Abstract

Increased concentrations of DNA-containing immune complexes in the serum are associated with systemic autoimmune diseases such as lupus. Stimulation of Toll-like receptor 9 (TLR9) by DNA is important in the activation of plasmacytoid dendritic cells and B cells. Here we show that HMGB1, a nuclear DNA-binding protein released from necrotic cells, was an essential component of DNA-containing immune complexes that stimulated cytokine production through a TLR9-MyD88 pathway involving the multivalent receptor RAGE. Moreover, binding of HMGB1 to class A CpG oligodeoxynucleotides considerably augmented cytokine production by means of TLR9 and RAGE. Our data demonstrate a mechanism by which HMGB1 and RAGE activate plasmacytoid dendritic cells and B cells in response to DNA and contribute to autoimmune pathogenesis.

Rights and Permissions

Citation: Nature Immunology 8, 487 - 496 (2007). doi:10.1038/ni1457

Related Resources

Link to article in PubMed

PubMed ID

17417641